ArticleThe Journal of biological chemistry2015
Structure-Function Analysis of the Mcl-1 Protein Identifies a Novel Senescence-regulating Domain.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed.
- Cellular senescence links muscle atrophy and posttraumatic osteoarthritis after ACL injury.Function (Oxford, England) · 2026Article
- Targeted Degradation of MCL-1 by PROTAC Mcl-1 Degrader-1 Exhibits Antiproliferative and Antimigratory Effects and Triggers Mitochondria-Mediated Apoptosis in Colorectal Cancer.Current issues in molecular biology · 2026Article
- Mcl1 as a Molecular Switch Linking Inflammatory Bowel Diseases to Colorectal Tumorigenesis.Biomolecules · 2026Review
- MCL1 may not mediate chemoresistance.bioRxiv : the preprint server for biology · 2025Article
- MCL-1 as a molecular switch between myofibroblastic and pro-angiogenic features of breast cancer-associated fibroblasts.Cell death & disease · 2025Article
- Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence.International journal of molecular sciences · 2023Review
- Targeting MCL-1 protein to treat cancer: opportunities and challenges.Frontiers in oncology · 2023Review
- Understanding MCL1: from cellular function and regulation to pharmacological inhibition.The FEBS journal · 2022Review
- Review
- Increased MCL-1 synthesis promotes irradiation-induced nasopharyngeal carcinoma radioresistance via regulation of the ROS/AKT loop.Cell death & disease · 2022Article
- MCL1 nuclear translocation induces chemoresistance in colorectal carcinoma.Cell death & disease · 2022Article
- Mcl-1 regulates reactive oxygen species via NOX4 during chemotherapy-induced senescence.Oncotarget · 2017Article
- Combination PD-1 blockade and irradiation of brain metastasis induces an effective abscopal effect in melanoma.OncoimmunologyArticle
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Unlike other antiapoptotic Bcl-2 family members, Mcl-1 also mediates resistance to cancer therapy by uniquely inhibiting chemotherapy-induced senescence (CIS). In general, Bcl-2 family members regulate apoptosis at the level of the mitochondria through a common prosurvival binding groove. Through mutagenesis, we determined that Mcl-1 can inhibit CIS even in the absence of its apoptotically important mitochondrion-localizing domains. This finding prompted us to generate a series of Mcl-1 deletion mutants from both the N and C termini of the protein, including one that contained a deletion of all of the Bcl-2 homology domains, none of which impacted anti-CIS capabilities. Through subsequent structure-function analyses of Mcl-1, we identified a previously uncharacterized loop domain responsible for the anti-CIS activity of Mcl-1. The importance of the loop domain was confirmed in multiple tumor types, two in vivo models of senescence, and by demonstrating that a peptide mimetic of the loop domain can effectively inhibit the anti-CIS function of Mcl-1. The results from our studies appear to be highly translatable because we discerned an inverse relationship between the expression of Mcl-1 and of various senescence markers in cancerous human tissues. In summary, our findings regarding the unique structural properties of Mcl-1 provide new approaches for targeted cancer therapy.
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Registered trials
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